Precision Neuromodulation for Early Intervention in Fibrosis Development

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Fibrosis is the major underlying cause for the onset of degenerative disease, associated with chronic inflammation and pain. There is currently neither a cure available, nor reliable means to stop disease progression. While degenerative diseases are often initiated by local stress or trauma that fails to heal, it is the unresolved inflammation that causes a system response that keeps on signalling that more inflammation is needed to overcome the local event. These signals are transmitted from the local tissue environment to the central nervous system (CNS) through the peripheral nervous system (PNS), and specifically the vagus nerve, which carries internal and external somatosensory feedback back to the CNS and exerts control over various body functions such as the immune system. While local, personalized cell-therapeutics can be used to enhance or improve the regenerative potential, this is not a solution that every patient has access to. Therefore, alternative solutions such as bioelectronic medicine are required, where a systemic approach may be more suitable and effective.

Vagus nerve stimulation (VNS) can modulate systemic inflammatory responses and could, in turn, impact tissue regeneration in fibrosis. However, current VNS approaches lack precise and spatially targeted stimulation, hindering therapeutic effectiveness without side effects. As a part of imec's Tenure Track initiative, this PhD project is focused on the development and validation of a novel VNS paradigm that supports multi-channel stimulation and recording in a pre-clinical rat model of osteoarthritis (OA). In this model, the VNS setup will be developed to allow spatially selective stimulation and closed-loop feedback strategies, which is a prerequisite for an optimized, adaptive treatment for individual subjects. By combining functional stimulation selectivity with advanced signal processing algorithms and real-time data analysis, the aim is to enhance stimulation effectiveness while minimizing side effects.